Detecting apparatus and associated kit and method

ABSTRACT

The invention concerns a detecting apparatus ( 12 ) comprising:—at least two sensors ( 24, 26, 28 ), with at least one sensor ( 24 ) being an ultrasound transducer adapted to produce ultrasound waves, and—a positioning device ( 16 ) defining several compartments ( 22 ), each compartment ( 22 ) being adapted to hold a sensor ( 24, 26, 28 ) and each compartment ( 22 ) being located at predetermined location, the positioning device ( 16 ) comprising a holder adapted to be fixed on the skull of a subject, the positioning device ( 16 ) being adapted to be maintained on the head of the subject using the holder.

TECHNICAL FIELD OF THE INVENTION

The present invention concerns a detecting apparatus. The invention alsorelates to a kit for forming such detecting apparatus and an associatedmethod for determining the locations of compartments adapted to hold asensor.

BACKGROUND OF THE INVENTION

In neuroscience, a number of devices have been developed to betterunderstand brain activity.

Usually, the developed device involves several imaging modalitiesallowing each to acquire a specific parameter of brain activity. Amongthe imaging modalities, it can be cited functional magnetic resonanceimaging (also named after the acronym fMRI) related to the BOLD effect,the optical imaging (such as optical absorption imaging, acousto-opticalimaging, photoacoustical imaging), functional ultrasound imaging (alsonamed fUltrasound) and electroencephalogram.

Documents US 2014/121520 A1, US 2014/107435 A1, CN 103 976 709 A and WO2014/155322 A1 illustrate that, in various field of medicine, systemshave been developed to image an area. As a specific example, document US2014/121520 A1 is relative to a system devoted to a patient's breast.

Nevertheless, these documents illustrate systems which are relative toarea wherein the events are reproducible. These systems are thus notapplicable for the brain because it is not anymore the case for thebrain.

Indeed, the above-mentioned imaging modalities operate independently andcannot be achieved on the same animal at the same time to the samefunctional event.

Therefore, in practice, the experiments on the “almost the same”functional event are repeated and then all parameters independentlyacquired are treated during a post-processing method. For example, it isdifficult to achieve on the same animal an fMRI imaging, coupled with aphotoacoustical imaging. But the knowledge of the parameters accessibleto such imaging modalities at the same time is crucial to understandingspecific diseases, such as epilepsy where knowledge of functional brainactivity measured by fMRI coupled with blood oxygenation level measuredby an optical imaging system is extremely interesting.

SUMMARY OF THE INVENTION

The invention aims at facilitating the imaging on the same subject.

To this end, the present specification describes a detecting apparatus,the detecting apparatus comprising :

-   -   at least two sensors, and    -   a positioning device defining several compartments, each        compartment being adapted to hold a sensor and each compartment        being located at predetermined location,

a sensor being an ultrasound transducer adapted to produce ultrasoundwaves.

Thanks to the invention, it becomes possible to image several locationson the same subject in a very easy way.

Indeed, such detecting apparatus is reconfigurable, which enables tomodify the position of the sensor without modifying the position of theposition device.

In addition, such detecting apparatus can be used for differentexperiences.

Moreover, such detecting apparatus can be useful in the cases ofbiological phenomena difficult to reproduce.

Notably, when the detecting apparatus comprises several sensors, severalimaging modalities operating independently can be achieved on the sameanimal at the same time to the same functional event.

According to further aspects of the invention which are advantageous butnot compulsory, the detecting apparatus might incorporate one or severalof the following features, taken in any technically admissiblecombination:

-   -   the positioning device is a frame having a periphery, the        predetermined locations being defined with reference to the        periphery.    -   the compartments are removable cases or embedded at different        locations.    -   the detecting apparatus further comprises removable spacers        having predetermined dimensions and adapted for guiding the        insertion of a sensor in a compartment.    -   the detecting apparatus comprises at least two sensors adapted        to measure different physical quantities.    -   the positioning device is a frame, the frame having a polygonal        shape delimited by sides, each side having a length inferior or        equal to 10 cm.    -   the detecting apparatus comprises at least three sensors, one        sensor being an ultrasound transducer, one sensor being an        accelerometer and one sensor being adapted to measure electrical        signals.    -   the positioning device comprises a holder adapted to be fixed on        the skull of an animal, the positioning device being adapted to        be maintained on the head of an animal using the holder.    -   the number of compartments is superior or equal to 100.    -   the compartments are arranged in a lattice.    -   the compartments are delimitated by intersecting bars, the        number of bars being superior or equal to 10.    -   each sensor has a sensing portion and a mechanical portion        adapted to maintain the sensing portion in position and, for        each sensor, the mechanical portion of one sensor has a shape        which is complementary to the shape of the mechanical portion(s)        of the other sensor(s).

The specification also relates to a kit for forming a detectingapparatus comprising:

-   -   a positioning device defining several compartments, each        compartment being adapted to hold a sensor and each compartment        being located at predetermined location,    -   a plurality of different sensors, and    -   a plurality of removable spacers having predetermined dimensions        and adapted for guiding the insertion of a sensor in a        compartment.    -   a plurality of removable spacers having predetermined dimensions        and adapted for guiding the insertion of a sensor in a        compartment and locking in place a sensor in a compartment.    -   one sensor is a printed multielectrode electroencephalography        foil.    -   one sensor is one or multiple implantable electroencephalography        electrodes.

The specification also relates to a method for determining the locationsof compartments adapted to hold a sensor comprising:

-   -   providing physical quantities to measure,    -   providing the area where the physical quantity is to be        measured,    -   providing a kit as previously described,    -   providing the individual dimensions of each element of the kit        as previously described, and    -   optimizing the locations of the compartments to fulfill a        predetermined criteria.

According to further aspects of the invention which are advantageous butnot compulsory, the method might incorporate one or several of thefollowing features, taken in any technically admissible combination:

-   -   the criteria is that the ratio of signal to noise of each sensor        be strictly superior to a given value.    -   the criteria is the total dimensions and weight of the detecting        apparatus formed when assembling the kit.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be better understood on the basis of the followingdescription which is given in correspondence with the annexed figuresand as an illustrative example, without restricting the object of theinvention. In the annexed figures:

FIG. 1 shows schematically a subject holding an example of detectingapparatus;

FIG. 2 shows schematically the detecting apparatus of FIG. 1;

FIG. 3 shows schematically a kit for forming the detecting apparatus ofFIG. 1;

FIG. 4 shows schematically another example of detecting apparatus thatcan be obtained with the kit of FIG. 3;

FIG. 5 shows schematically another example of detecting apparatus;

FIG. 6 shows schematically another example of detecting apparatus, and

FIG. 7 shows schematically another example of detecting apparatus.

DETAILED DESCRIPTION OF SOME EMBODIMENTS

A subject 10 and a detecting apparatus 12 are illustrated on FIG. 1.

The subject 10 is a mouse.

More generally, the subject 10 is an animal for which at least onespecific area is to be analyzed.

The specific area to be analyzed depends, for instance, of the kind ofbiological problem that is to be studied.

As an illustration, when the biological problem is memory, the area is aspecific area of the hippocampus.

For the remainder of the specification, for illustrative purpose only,it is considered that the mouse suffers from epilepsy and that the areasto be analyzed are areas of the brain.

For this, the subject 10 has a head 14, the detecting apparatus 12 beingmaintained on the head of the subject 10.

The detecting apparatus 12 is an apparatus adapted to detect at leastone physical value in the areas of the brain of the subject 10.

The detecting apparatus 12 comprises a positioning device 16, threesensors 24, 26, 28 and three spacers 30, 32, 34.

The positioning device 16 illustrated in the example of FIG. 2 is aframe with a periphery 18 and intersecting bars 20.

According to the example illustrated, the frame has a polygonal shapedelimited by sides.

As an example, the polygonal shape is a square. Each side has the samelength.

For an animal considered as small, such as a rat or a mouse, the lengthof a side is equal to the length of the brain of the animal. Forinstance, the length is 1 centimeter when the subject 10 is a mouse orthe length is 2 centimeters when the subject 10 is a rat.

For an animal considered as big, such as a human, the length of a sideis equal to a portion of the length of the brain of the animal. Forinstance, the length of the side is inferior to 10 centimeters.

More generally, the length of a side is equal to the minimum of thelength of the brain of the animal and 10 centimeters.

For the specific case of FIG. 1, each side has a length inferior orequal to 10 centimeters (cm).

The intersecting bars 20 constitute a grid.

The number of bars 20 is superior or equal to 10.

In the specific example of FIG. 2, ten horizontal bars 20 and tenvertical bars 20 are illustrated.

Accordingly, ten rows and ten columns can be defined with the periphery18.

In the remainder of the specification, the rows are labeled L with anumber so that each row is labeled L1, L2, L3, L4, L5, L6, L7, L8, L9 orL10.

Similarly, in the remainder of the specification, the columns arelabeled C with a number so that each column is labeled C1, C2, C3, C4,C5, C6, C7, C8, C9 or C10.

In addition, the words “up” and “down” on the one hand and “left” and“right” on the other hand are defined with reference respectively to therows L1, L2, L3, L4, L5, L6, L7, L8, L9, L10 and to the columns C1, C2,C3, C4, C5, C6, C7, C8, C9, C10.

It will be consider that the less high the number associated to the rowL1, L2, L3, L4, L5, L6, L7, L8, L9, L10 is the upper the row L1, L2, L3,L4, L5, L6, L7, L8, L9, L10 is. In other words, the first row L1 isabove the second row L2 while the second row L2 is below the first rowL1. Similarly, the first column C1 is on the left of the second columnC2 while the second column C2 is on the right of the first column C1.

The intersecting bars 20 are delimitating compartments 22 which aredefined for the positioning device 16.

In the illustrated example, the positioning device defines a number ofcompartments 22 which is equal to 100.

More generally, the positioning device 16 defines a number ofcompartments 22 which is superior or equal to 100.

Each compartment 22 is adapted to hold a sensor.

Each compartment 22 is located at a predetermined location.

In the illustrated example, the predetermined locations are defined withreference to the periphery 18.

For instance, each compartment 22 can be linked in a one-to-one mannerto two coordinates: one row coordinate and one column coordinate. As anexample, the compartment 22 belonging to the first row L1 and the firstcolumn C1 is a neighbor for the compartment 22 belonging to the firstrow L1 and the second column C2, the compartment 22 belonging to thesecond row L2 and the first column C1 and the compartment 22 belongingto the second row L2 and the second column C2.

In such specific case, the compartments 22 are arranged in a lattice.Such lattice is a regular lattice.

In addition, the spatial distance between two adjacent predeterminedlocations is inferior or equal to 100 μm.

Preferably, the spatial distance between two adjacent predeterminedlocations is inferior or equal to 10 μm.

For instance, for each compartment 22, a center is defined. Thepredetermined location of a compartment 22 then corresponds to thecenter of the considered compartment 22. In such context, the spatialdistance between two predetermined locations is defined as the distancebetween the corresponding centers.

Furthermore, the positioning device 16 comprises a holder.

The positioning device is adapted to be maintained on the head 14 of thesubject 10 using the holder.

This means that the holder is adapted to be fixed on the skull of thesubject 10.

The first sensor 24 is an ultrasound transducer adapted to produceultrasound waves.

According to a specific example, the first sensor 24 is a high frequencyultrasound transducer. In such case, the first sensor 24 is a lineararray adapted to operate at a frequency around 15 MHz (MegaHertz).

The first sensor 24 is used mainly to detect cerebral blood volume andflow through Doppler sequences or contrast agents.

The first sensor 24 is located on the second column C2 and on the ninthrow L9.

More precisely, the first sensor 24 is located on the upper part on theright of the compartment 22 belonging to the second column C2 and theninth row L9.

The second sensor 26 is an accelerometer.

An accelerometer is adapted to measure proper acceleration of theanimal. The accelerometer can be used to detect the state of the animal.The state of the animal is, for instance sleeping, running or eating.The knowledge of such state is, for example, useful for behavorialstudies.

The second sensor 26 is located on the second column C2 and on the sixthrow L6.

More precisely, the second sensor 26 is located on the right of thecompartment 22 belonging to the second column C2 and the sixth row L6.

The third sensor 28 is adapted to measure electrical signals.

For instance, the third sensor 28 is a voltmeter.

According to other embodiments, the third sensor 28 is a surfaceelectrode, an implanted electrode or an array of such electrodes.

The third sensor 28 is located on the second column C2 and on the thirdrow L3.

More precisely, the third sensor 28 is located on the upper part on theright of the compartment 22 belonging to the second column C2 and thethird row L3.

Each spacer 30, 32, 34 is removable.

By “removable”, it is meant that each spacer 30, 32, 34 can be placed ata specific location and then moved to another location.

Each spacer 30, 32, 34 has predetermined dimensions.

The first spacer 30 has a parallelepiped shape, the first spacer 30occupying half a column along one dimension and two rows according tothe other dimension.

The second spacer 32 has a parallelepiped shape, the second spacer 32occupying one column and a half along one dimension and ten rowsaccording to the other dimension.

The third spacer 34 has a parallelepiped shape, the third spacer 32occupying three columns along one dimension and two rows according tothe other dimension.

Each spacer 30, 32, 34 is adapted for guiding the insertion of a sensorin a compartment 22.

In the illustrated example of FIG. 2, the first spacer 30 is on theright of the compartments 22 belonging respectively to the second columnC2 and the fifth row L5 and to the second column C2 and the sixth rowL6.

The first spacer 30 is adapted to guide the first sensor 24 and thesecond sensor 26.

The second spacer 32 is situated on the first column C1 and on the leftof the second column C2.

The second spacer 32 is adapted to guide each sensor 24, 26 and 28.

As can be seen on FIG. 2, the third spacer 34 is on the compartments 22belonging respectively to the third column C3 and the first row L1, tothe third column C3 and the second row L2, to the fourth column C4 andthe first row L1, to the fourth column C4 and the second row L2. Thethird spacer 34 is also located on the right of the compartments 22belonging to the second column C2 and the first row L1 and to the secondcolumn C2 and the second row L2. The third spacer 34 is also located onthe left of the compartments 22 belonging to the fifth column C5 and thefirst row L1 and to the fifth column C5 and the second row L2.

The third spacer 34 is adapted to guide the third sensor 28.

The detecting apparatus 12 is reconfigurable as can be illustrated onthe kit 40 for forming detecting apparatuses 12 which is illustrated onFIG. 3.

The kit 40 comprises the positioning device 16, a sensor bag 42 and aspacer bag 44.

The sensor bag 42 comprises the first sensor 24, the second sensor 26,the third sensor 28 and a fourth sensor 46.

According to this specific embodiment, the fourth sensor 46 is atemperature sensor.

Alternatively, the fourth sensor 46 is an optical sensor.

The spacer bag 44 comprises the three spacers 30, 32 and 34.

Operation of the kit 40 is now described in reference to an example ofcarrying out of a method for determining the locations of compartments22 being adapted to hold a sensor.

The method comprises a step of providing physical quantities to measure.

For instance, it may be desired to measure the temperature, the bloodflux, the proper acceleration and electric activity.

The method comprises a step of providing the area where each physicalquantity is to be measured.

In the example illustrated, the area is a spatial zone of the brain ofthe subject 10.

The method comprises a step of providing the kit 40.

The method also comprises a step of providing the individual dimensionsof each element 16, 24, 26, 28, 30, 32, 34 and 46 of the kit 40.

For instance, for the first spacer 30, the following data are provided:the first spacer 30 has a parallelepiped shape, the first spacer 30occupying half a column along one dimension and two rows according tothe other dimension.

The method also comprises a step of optimizing the locations of thecompartments 22 to fulfill a predetermined criteria.

By way of an illustration, the optimizing step is performed by a seriesof iterations in an optimization program. The goal of this optimizationprogram, starting from an initial configuration of the locations is toobtain a configuration of locations of the compartments 22 that conferto the detecting apparatus 12 a property that as much as possiblefulfills the criteria.

For this, a cost function C representative of deviations of thedetecting apparatus 12 from the ideal apparatus fulfilling the criteriais used.

The cost function C is a positive function that should be minimizedduring the step of optimizing.

In order to proceed with performing this minimization, it is sufficientto start from initial configuration of the locations and to use acalculation method that provides the ability to reduce by iterations thevalue of the cost function C.

As illustration, the calculation method used is a damped least squaresmethod (often referred to by the English acronym DLS for “dampedleast-squares”).

The configuration of locations of the compartments 22 are thus obtainedafter iterations of the optimization program.

The predetermined criteria to be considered at the step of optimizingis, for instance, that the ratio of signal to noise of each sensor 24,26, 28 and 46 be strictly superior to a given value.

Alternatively, the predetermined criteria is the total dimensions andweight of the kit 40 when assembled. In other words, the predeterminedcriteria is the total dimensions and weight of the detecting apparatus12 formed when assembling the kit 40.

Then, with the configuration of locations of the compartments 22, a newdetecting apparatus 12 may be obtained.

FIG. 4 illustrates another example of detecting apparatus 12 that can beobtained.

The detecting apparatus 12 comprises the positioning device 16 and thefour sensors 24, 26, 28 and 46.

In this specific embodiment, the detecting apparatus 12 does notcomprise any spacer.

The first sensor 24 is located on the fifth column C5 and on the secondrow L2.

More precisely, the first sensor 24 is located on the upper part on theleft of the compartment 22 belonging to the fifth column C5 and on thesecond row L2.

The third sensor 26 is located on the first column C1 and on the sixthrow L6.

More precisely, the third sensor 26 is located on the upper part on theright of the compartment 22 belonging to the first column C1 and on thesixth row L6.

The third sensor 28 is located on the first column C1 and on the secondrow L2.

More precisely, the third sensor 28 is located on the upper part on theleft of the compartment 22 belonging to the first column C1 and on thesecond row L2.

The fourth sensor 46 is located on the tenth column 010 and on the sixthrow L6.

More precisely, the fourth sensor 46 is located on the upper part on theright of the compartment 22 belonging to the tenth column 010 and on thesixth row L6.

It should be understood that multiple detecting apparatus 12 areobtainable with the kit 40.

According to another embodiment, the detecting apparatus 12 comprisesonly two sensors.

In such case, preferably, the two sensors are adapted to measuredifferent physical quantities

Alternatively, more than one sensor is an ultrasound transducer.

In other word, it becomes possible to image several locations on thesame subject 10 in a very easy way.

Indeed, the detecting apparatus 12 is reconfigurable, which enables tomodify the position of the sensors 24, 26, 28 and 46 without modifyingthe position of the position device 16.

In addition, such detecting apparatus 12 can be used for differentexperiences.

Moreover, such detecting apparatus 12 can be useful in the cases ofbiological phenomena difficult to reproduce.

For instance, thanks to such detecting apparatus 12, several differentphysical quantities can be measured simultaneously on the same subject10 when this subject 10 is facing an epilepsy crisis.

FIGS. 5 to 7 illustrates other examples of detecting apparatuses thatmay be considered.

On FIG. 5, a detecting apparatus 112 is illustrated.

The detecting apparatus 112 comprises a positioning device 116 which isa frame with a periphery 118.

The detecting apparatus 112 comprises a first ultrasound probe 120 and asecond ultrasound probe 122.

The detecting apparatus 112 comprises removable spacers 130, 132, 134,136 and 138.

The remarks made for an element with reference to FIG. 1 apply in asimilar to the same element in the embodiment of FIG. 5.

The detecting apparatus 112 combines both ultrasound probes 120 and 122over different selected brain areas. For example, the sensors 120 and122 are positioned using spacers 130, 132, 134, 136 and 138.

On FIG. 6, another detecting apparatus 212 is illustrated.

The detecting apparatus 212 comprises a positioning device 216 which isa frame with a periphery 218 and a grid 220.

The detecting apparatus 212 comprises an ultrasound probe 222 and animplanted electrode array 224.

The detecting apparatus 212 also comprises rods 230 for positioning thesensors 222 and 224.

The remarks made for an element with reference to FIG. 1 apply in asimilar to the same element in the embodiment of FIG. 6.

The detecting apparatus 212 combines the ultrasound probe 222 and theimplanted electrode array 224 in the context of epilepsy monitoring onawake rats. For example, the sensors 222 and 224 are positioned usingthe rods 230 on the grid 220.

On FIG. 7, another detecting apparatus 312 is schematically shown.

The detecting apparatus 312 comprises a positioning device 326 which isa frame. The frame is obtained by three-dimensional printing. Suchtechnique is a specific example of rapid prototyping technique.

The detecting apparatus 312 further comprises two ultrasound probes 330,332, one accelerometer 334 and one surface electrode 336.

Each sensor 330, 332, 334 and 336 are embedded in the printed frame.

The remarks made for an element with reference to FIG. 1 apply in asimilar to the same element in the embodiment of FIG. 7.

The detecting apparatus 312 is, for instance, usable in the context offunctional connectivity and behavioral study in awake mice.

According to another example, each sensor 24, 26, 28 has a sensingportion and a mechanical portion adapted to maintain the sensing portionin position. In addition, for each sensor, the mechanical portion of onesensor 24, 26, 28 has a shape which is complementary to the shape of themechanical portions of the other sensors 24, 26, 28.

In other words, the cooperation between two mechanical portions of twodifferent sensors 24, 26, 28 enables to maintain each sensing portion inposition and to reduce the congestion.

For instance, each mechanical portion has a recess and a protusion, theshape of the protusion being complementary to the shape of the recess.Thus, the protusion of one mechanical portion can be inserted in therecess of the adjacent mechanical portion so as to enable themaintaining of each sensor 24, 26, 28. In addition, in such example, themechanical portion can be identical which results in an easierfabrication.

In such embodiment, each sensor 24, 26, 28 can be imbricated one inanother.

According to a specific embodiment, one sensor 24 is an ultrasoundtransducer while one sensor 26 is a printed multielectrodeelectroencephalography (EEG) foil. The foil is positioned below theultrasound transducer compartment, that is nearer to the area to besensed.

In this case, the foil is proximal to the brain while the ultrasoundtransducer is distal to the brain. In such context, proximal and distalare defined with relation to the brain. In other words, a proximalelement is nearer to the brain than a distal element.

According to another embodiment, one sensor 24 is an ultrasoundtransducer while one sensor 26 is one or multiple implantableelectroencephalography (EEG) electrodes.

These electrodes are guided obliquely inside the brain. In addition,these electrodes are below the ultrasound transducer compartment, whichmeans nearer to the area to be sensed.

In this case, the electrodes are proximal to the brain while theultrasound transducer is distal to the brain. In such context, proximaland distal are defined with relation to the brain. In other words, aproximal element is nearer to the brain than a distal element.

The embodiments and alternative embodiments considered here-above can becombined to generate further embodiments of the invention.

In addition, the detecting apparatus 12 may be used for various uses.

Three uses are developed below.

First Use: Imaging a Specific Area of the Brain of a Mobile Rat with aCamera

According to the first use, the detecting apparatus 12 is adapted toimage a specific plane of the mobile rat with an embedded camera.

A frame is implanted on a rat with screws and dental cement. The skullof the rat is rendered thinner or opened on a window.

In a first embodiment, the position of the frame is determined beforethanks to an anatomical frame. Superficial veins of the brain or skullsuture lines are examples of anatomical frame.

According to another embodiment, after putting the frame on the skull ofthe rat, the precise location of the frame is determined thanks to ananatomical frame, such as superficial veins of the brain as previouslyproposed.

According to still another embodiment, after putting the frame on theskull of the rat, the precise location of the frame is determined thanksto a specific sensor. This specific sensor has a known position withrelation to the frame. Such known position can be obtained by using acompartment adapted to hold the sensor. In specific cases, thecompartment is translated to obtain a more precise estimation of theposition of the frame.

The area to be imaged is then determined. As an example, the determinedarea is the visual cortex.

The kind of additional sensor to be fixed and the associated locationare chosen.

As an example, the additional sensor is a camera.

In variant, the additional sensor is an accelerometer or a microphone.

According to the case, the additional sensor is put on the compartmentcorresponding to the chosen associated location or the additional sensoris put in a removable case which is then positioned at the associatedlocation.

If a removable case is used, the detecting apparatus 12 only comprisesthe additional sensor during the experiment which enables the rat tomove relatively freely.

The only constraint is that the rat moves with the frame.

In such first use, the detecting apparatus 12 has two sensors: a probeand a camera. The probe is positioned in a stereotactic way withrelation to the brain of the rat. The position of the camera, and moregenerally the second sensor, is reconfigurable as well as the choice ofthe nature of the sensor. The position of the second sensor isdetermined by using the position of the first sensor. It should be notedthat the position of the second sensor may be subjected to less strictconstraints that the position of the first sensor in so far as the areato be imaged may be relatively large whereas the position of the firstsensor is imposed a stereotactic way with relation to the brain of therat

Second Use: Imaging Two Specific Areas of the Brain of a Mobile Rat withTwo Probes

According to the second use, two planes of the brain of a mobile rat areimaged with two ultrasound probes.

A frame is implanted on a rat with screws and dental cement. The skullof the rat is rendered thinner or opened on a window.

In a first embodiment, the position of the frame is determined beforethanks to an anatomical frame. Superficial veins of the brain or skullsuture lines are examples of anatomical frame.

According to another embodiment, after putting the frame on the skull ofthe rat, the precise location of the frame is determined thanks to ananatomical frame, such as superficial veins of the brain as previouslyproposed.

According to still another embodiment, after putting the frame on theskull of the rat, the precise location of the frame is determined thanksto a specific sensor. This specific sensor has a known position withrelation to the frame. Such known position can be obtained by using acompartment adapted to hold the sensor. In specific cases, thecompartment is translated to obtain a more precise estimation of theposition of the frame.

The areas to be imaged are then determined. As an example, thedetermined area can be the visual cortex and the olfactory bulb.

For this second use, it is assumed that several compartments arepositioned in a stereotactic way with relation to the brain of the rat.

According to an embodiment, such compartments are not removable and arepositioned with the frame.

According to another embodiment, the compartments are removable and arepositioned by using one of the previous proposed methods for positioningthe frame. As an example, the precise location of a compartment isdetermined thanks to a specific sensor

The ultrasound probes are assembled in a transitory way with thecompartments which correspond to the desired location.

This enables to cumulate several advantages.

On the one hand, the rat only holds the ultrasound probes during theexperiment.

On the other hand, both the frame and the ultrasound probes arepositioned in a stereotactic way with relation to the brain of the rat.

In other words, the use of the detecting apparatus 12 in such contextreally renders carrying out an in vivo experiment on the brain of a rateasier for the scientist, without loss of precision in the measurementsto be achieved on the rat.

Third Use: Imaging a Unique Area of the Brain of a Mobile Mouse andUsing an Array of Surface EEG Multielectrodes Such as Printed Foil

According to the third use, only one plane of the brain of a mobilemouse is imaged with a probe while enabling the simultaneous use of anarray of surface EEG multielectrodes.

A frame is implanted on a mouse with screws and dental cement. The skinof the mouse is removed.

In a first embodiment, the position of the frame is determined beforethanks to an anatomical frame. Superficial veins of the brain or skullsuture lines are examples of anatomical frame.

According to another embodiment, after putting the frame on the skull ofthe mouse, the precise location of the frame is determined thanks to ananatomical frame, such as superficial veins of the brain as previouslyproposed.

According to still another embodiment, after putting the frame on theskull of the mouse, the precise location of the frame is determinedthanks to a specific sensor. This specific sensor has a known positionwith relation to the frame. Such known position can be obtained by usinga compartment adapted to hold the sensor. In specific cases, thecompartment is translated to obtain a more precise estimation of theposition of the frame.

The area to be imaged is then determined. As an example, the determinedarea is the hippocampus. The ultrasound probe is assembled in atransitory way with the compartment which corresponds to the desiredlocation.

For this third use, it is assumed that a second compartment adapted toreceive an array of surface EEG multielectrodes such as printed foil isfirst positioned in a stereotactic way with relation to the brain of themouse and then glued with a mix of EEG paste and glue to the skull.

According to an embodiment, such printed foil is positioned with theframe below the ultrasound probe compartment.

In variant, the additional sensor is an EEG electrode that is guidedobliquely inside the brain below the ultrasound probe.

In this third use, the same advantages as detailed for the second usestill apply.

In each use, it appears that the detecting apparatus 12 has two maininterests which may be cumulated in the use.

The first interest is the fact that the detecting apparatus 12 isreconfigurable by construction which enables to change the detectingapparatus 12 easily for the scientist.

One advantage is that each additional sensor can be chosen and/orpositioned according to the specific needs of the experiment.

One advantage resulting from such reconfigurability is that the weightapplied on the skull of the rat is limited to the time of acquisition.The useful sensor(s) is only hold for a limited time.

The second interest is the fact that the detecting apparatus 12 isadapted for achieving brain imaging of a small animal, such as a rat.

Notably, the detecting apparatus 12 enables to ensure that severalsensors are positioned in a stereotactic way with relation to the brainof the rat.

This positioning in a stereotactic way is in addition compatible withthe movement of the rat.

1. Detecting apparatus comprising: at least two sensors, with at leastone sensor being an ultrasound transducer adapted to produce ultrasoundwaves, and a positioning device defining several compartments, eachcompartment being adapted to hold a sensor and each compartment beinglocated at predetermined location, the positioning device comprising aholder adapted to be fixed on the skull of a subject, the positioningdevice being adapted to be maintained on the head of the subject usingthe holder.
 2. Detecting apparatus according to claim 1, wherein thecompartments are removable cases or embedded at different locations. 3.Detecting apparatus according to claim 1, wherein the positioning deviceis a frame having a periphery, the predetermined locations being definedwith reference to the periphery.
 4. Detecting apparatus according toclaim 1, wherein the detecting apparatus further comprises removablespacers having predetermined dimensions and adapted for guiding theinsertion of a sensor in a compartment.
 5. Detecting apparatus accordingto claim 1, wherein the detecting apparatus comprises at least twosensors adapted to measure different physical quantities.
 6. Detectingapparatus according to claim 1, wherein the positioning device is aframe, the frame having a polygonal shape delimited by sides, each sidehaving a length inferior or equal to 10 centimeters.
 7. Detectingapparatus according to claim 1, wherein the detecting apparatuscomprises at least three sensors, one sensor being an ultrasoundtransducer, one sensor being an accelerometer and one sensor beingadapted to measure electrical signals.
 8. Detecting apparatus accordingto claim 1, wherein one sensor is a printed multielectrodeelectroencephalography foil.
 9. Detecting apparatus according to claim1, wherein one sensor is one or multiple implantableelectroencephalography electrodes.
 10. Detecting apparatus according toclaim 1, wherein the compartments are arranged in a lattice. 11.Detecting apparatus according to claim 10, wherein the compartments aredelimitated by intersecting bars, the number of bars being superior orequal to
 10. 12. Detecting apparatus according to claim 1, wherein eachsensor has a sensing portion and a mechanical portion adapted tomaintain the sensing portion in position and wherein, for each sensor,the mechanical portion of one sensor has a shape which is complementaryto the shape of the mechanical portion(s) of the other sensor(s). 13.Kit for forming a detecting apparatus comprising: a positioning devicedefining several compartments, each compartment being adapted to hold asensor and each compartment being located at predetermined location, aplurality of different sensors, and a plurality of removable spacershaving predetermined dimensions and adapted for guiding the insertion ofa sensor in a compartment.
 14. Method for determining the locations ofcompartments adapted to hold a sensor comprising: providing physicalquantities to measure, providing the area where the physical quantity isto be measured, providing a kit according to claim 13, providing theindividual dimensions of each element of the kit according to claim 13,and optimizing the locations of the compartments to fulfill apredetermined criteria.
 15. Method according to claim 14, wherein thecriteria is that the ratio of signal to noise of each sensor be strictlysuperior to a given value.
 16. Method according to claim 14, wherein thecriteria is the total dimensions and weight of the detecting apparatusformed when assembling the kit.